Aerosols impact climate, human health, and the chemistry of the atmosphere, and aerosol pH plays a major role in the physicochemical properties of the aerosol. However, there remains uncertainty as ...to whether aerosols are acidic, neutral, or basic. In this research, we show that the pH of freshly emitted (nascent) sea spray aerosols is significantly lower than that of sea water (approximately four pH units, with pH being a log scale value) and that smaller aerosol particles below 1 μm in diameter have pH values that are even lower. These measurements of nascent sea spray aerosol pH, performed in a unique ocean-atmosphere facility, provide convincing data to show that acidification occurs "across the interface" within minutes, when aerosols formed from ocean surface waters become airborne. We also show there is a correlation between aerosol acidity and dissolved carbon dioxide but no correlation with marine biology within the seawater. We discuss the mechanisms and contributing factors to this acidity and its implications on atmospheric chemistry.
The wound healing process that occurs after spinal cord injury is critical for maintaining tissue homeostasis and limiting tissue damage, but eventually results in a scar-like environment that is not ...conducive to regeneration and repair. A better understanding of this dichotomy is critical to developing effective therapeutics that target the appropriate pathobiology, but a major challenge has been the large cellular heterogeneity that results in immensely complex cellular interactions. In this study, we used single-cell RNA sequencing to assess virtually all cell types that comprise the mouse spinal cord injury site. In addition to discovering novel subpopulations, we used expression values of receptor-ligand pairs to identify signaling pathways that are predicted to regulate specific cellular interactions during angiogenesis, gliosis, and fibrosis. Our dataset is a valuable resource that provides novel mechanistic insight into the pathobiology of not only spinal cord injury but also other traumatic disorders of the CNS.
Several lines of evidence indicate that the advent of oxygenic photosynthesis preceded the oxygenation of the atmosphere—perhaps by as much as 300million years. The fate of biogenic O2 prior to its ...appearance in the atmosphere remains speculative, but recent work suggests that O2 was locally available within the surface ocean to support aerobic microbial ecosystems. Simple mass balance predicts that locally oxygenated environments (oxygen oases) could exist in areas of high productivity if the local rate of O2 production by oxygenic photosynthesis exceeded the combined rate of O2 loss by a number of processes (e.g., exchange with the atmosphere, transport within the ocean, reaction with reduced aqueous species, biological consumption). The areal extent of these environments and the dissolved O2 concentrations that could have persisted in an otherwise anoxic ocean, however, are key uncertainties in our understanding of the spatiotemporal redox-evolution of the early earth system.
We use an earth system model of intermediate complexity that has been modified to simulate a theoretical Archean biosphere in order to explore redox heterogeneity in the late Archean surface ocean. We demonstrate that oxygen oases are an expected consequence of oxygenic photosynthesis beneath an essentially O2-devoid atmosphere—and that oxygenated surface waters need not be restricted to shallow coastal environments or microbial mats. Within oxygen oases, O2 concentrations locally approach ~1–10μM for a large range of plausible Archean conditions. Although O2 concentrations in the open ocean are exceedingly low, biologically relevant dissolved O2 concentrations are widespread in our hypothetical surface ocean.
•Oxygenic photosynthesis generates oxygen oases under late Archean conditions.•Oxygen oases are large-scale, steady state features of the pelagic surface ocean.•Up to ~1–10μM O2 is possible locally in an otherwise essentially anoxic world.•Aerobic metabolism could have been widespread in a broadly anoxic Archean ocean.
Mammals have extremely limited regenerative capabilities; however, axolotls are profoundly regenerative and can replace entire limbs. The mechanisms underlying limb regeneration remain poorly ...understood, partly because the enormous and incompletely sequenced genomes of axolotls have hindered the study of genes facilitating regeneration. We assembled and annotated a de novo transcriptome using RNA-sequencing profiles for a broad spectrum of tissues that is estimated to have near-complete sequence information for 88% of axolotl genes. We devised expression analyses that identified the axolotl orthologs of cirbp and kazald1 as highly expressed and enriched in blastemas. Using morpholino anti-sense oligonucleotides, we find evidence that cirbp plays a cytoprotective role during limb regeneration whereas manipulation of kazald1 expression disrupts regeneration. Our transcriptome and annotation resources greatly complement previous transcriptomic studies and will be a valuable resource for future research in regenerative biology.
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•Creation of a transcriptome with near-complete sequence data for 88% of axolotl genes•Expression analyses identify tissue-enriched transcripts for key tissues•The RNA-binding protein cirbp plays a cytoprotective role in limb regeneration•Knockdown and overexpression of kazald1 in blastema cells impair limb regeneration
Discovery of genes driving axolotl limb regeneration has been challenging, due to limited genomic resources. Bryant et al. have created a transcriptome with near-complete sequence information for most axolotl genes, identified transcriptional profiles that distinguish blastemas from differentiated limb tissues, and uncovered functional roles for cirbp and kazald1 in limb regeneration.
Vinculin (Vcn) is a ubiquitously expressed cytoskeletal protein that links transmembrane receptors to actin filaments, and plays a key role in regulating cell adhesion, motility, and force ...transmission. Metavinculin (MVcn) is a Vcn splice isoform that contains an additional exon encoding a 68-residue insert within the actin binding tail domain. MVcn is selectively expressed at sub-stoichiometic amounts relative to Vcn in smooth and cardiac muscle cells. Mutations in the MVcn insert are linked to various cardiomyopathies. In vitro analysis has previously shown that while both proteins can engage filamentous (F)-actin, only Vcn can promote F-actin bundling. Moreover, we and others have shown that MVcn can negatively regulate Vcn-mediated F-actin bundling in vitro. To investigate functional differences between MVcn and Vcn, we stably expressed either Vcn or MVcn in Vcn-null mouse embryonic fibroblasts. While both MVcn and Vcn were observed at FAs, MVcn-expressing cells had larger but fewer focal adhesions per cell compared to Vcn-expressing cells. MVcn-expressing cells migrated faster and exhibited greater persistence compared to Vcn-expressing cells, even though Vcn-containing FAs assembled and disassembled faster. Magnetic tweezer measurements on Vcn-expressing cells show a typical cell stiffening phenotype in response to externally applied force; however, this was absent in Vcn-null and MVcn-expressing cells. Our findings that MVcn expression leads to larger but fewer FAs per cell, in conjunction with the inability of MVcn to bundle F-actin in vitro and rescue the cell stiffening response, are consistent with our previous findings of actin bundling deficient Vcn variants, suggesting that deficient actin-bundling may account for some of the differences between Vcn and MVcn.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We examined school days missed for routine dental care versus dental pain or infection to determine the relationship between children's oral health status and school attendance and performance.
We ...used 2008 data from the North Carolina Child Health Assessment and Monitoring Program. The study sample, weighted to reflect the state's population, included 2183 schoolchildren. Variables assessed included school absences and performance, oral health status, parental education, health insurance coverage, race, and gender.
Children with poor oral health status were nearly 3 times more likely (odds ratio = 3.89; 95% confidence interval = 1.96, 7.75) than were their counterparts to miss school as a result of dental pain. Absences caused by pain were associated with poorer school performance (P < .05), but absences for routine care were not. Mediation analyses revealed that oral health status was associated with performance independent of absence for pain.
Children with poorer oral health status were more likely to experience dental pain, miss school, and perform poorly in school. These findings suggest that improving children's oral health status may be a vehicle to enhancing their educational experience.
Modifications to the global run-on and sequencing (GRO-seq) protocol that enrich for 5'-capped RNAs can be used to reveal active transcriptional regulatory elements (TREs) with high accuracy. Here, ...we introduce discriminative regulatory-element detection from GRO-seq (dREG), a sensitive machine learning method that uses support vector regression to identify active TREs from GRO-seq data without requiring cap-based enrichment (https://github.com/Danko-Lab/dREG/). This approach allows TREs to be assayed together with gene expression levels and other transcriptional features in a single experiment. Predicted TREs are more enriched for several marks of transcriptional activation—including expression quantitative trait loci, disease-associated polymorphisms, acetylated histone 3 lysine 27 (H3K27ac) and transcription factor binding—than those identified by alternative functional assays. Using dREG, we surveyed TREs in eight human cell types and provide new insights into global patterns of TRE function.
Mechanochemical transduction enables an extraordinary range of physiological processes such as the sense of touch, hearing, balance, muscle contraction, and the growth and remodelling of tissue and ...bone. Although biology is replete with materials systems that actively and functionally respond to mechanical stimuli, the default mechanochemical reaction of bulk polymers to large external stress is the unselective scission of covalent bonds, resulting in damage or failure. An alternative to this degradation process is the rational molecular design of synthetic materials such that mechanical stress favourably alters material properties. A few mechanosensitive polymers with this property have been developed; but their active response is mediated through non-covalent processes, which may limit the extent to which properties can be modified and the long-term stability in structural materials. Previously, we have shown with dissolved polymer strands incorporating mechanically sensitive chemical groups-so-called mechanophores-that the directional nature of mechanical forces can selectively break and re-form covalent bonds. We now demonstrate that such force-induced covalent-bond activation can also be realized with mechanophore-linked elastomeric and glassy polymers, by using a mechanophore that changes colour as it undergoes a reversible electrocyclic ring-opening reaction under tensile stress and thus allows us to directly and locally visualize the mechanochemical reaction. We find that pronounced changes in colour and fluorescence emerge with the accumulation of plastic deformation, indicating that in these polymeric materials the transduction of mechanical force into the ring-opening reaction is an activated process. We anticipate that force activation of covalent bonds can serve as a general strategy for the development of new mechanophore building blocks that impart polymeric materials with desirable functionalities ranging from damage sensing to fully regenerative self-healing.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Remyelination failure is a crucial component of disease progression in the autoimmune demyelinating disease Multiple Sclerosis (MS). The regenerative capacity of oligodendrocyte progenitor cells ...(OPCs) to replace myelinating oligodendrocytes is likely influenced by many aspects of the lesion environment including inflammatory signaling and extracellular matrix (ECM) deposition. These features of MS lesions are typically attributed to infiltrating leukocytes and reactive astrocytes. Here we demonstrate that fibroblasts also contribute to the inhibitory environment in the animal model of MS, experimental autoimmune encephalomyelitis (EAE). Using Col1α1GFP transgenic mice, we show that perivascular fibroblasts are activated in the spinal cord at EAE onset, and infiltrate the parenchyma by the peak of behavioral deficits where they are closely associated with areas of demyelination, myeloid cell accumulation, and ECM deposition. We further show that both fibroblast conditioned media and fibroblast ECM inhibit the differentiation of OPCs into mature oligodendrocytes. Taken together, our results indicate that the fibrotic scar is a major component of EAE pathology that leads to an inhibitory environment for remyelination, thus raising the possibility that anti-fibrotic mechanisms may serve as novel therapeutic targets for MS.
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•Fibrosis is a prominent pathological feature of EAE lesions.•Col1α1-positive perivascular fibroblasts are the major source of fibrosis after EAE.•Fibrosis is closely associated with demyelinated regions.•Fibroblast ECM and conditioned media inhibit OPC differentiation in vitro.
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